Synthesis, structure, and antiparasitic activity of sulfamoyl derivatives of ribavirin.
The triazole nucleoside derivatives 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-carboxamide (2), 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl) [1,2,4]triazole-3-thiocarboxamide (3), and 1-(5'-O-sulfamoyl-beta-D-ribofuranosyl)-[1,2,4]triazole-3- carbonitrile (4) were synthesized. Suitably protected triazole nucleosides were converted to their corresponding 5'-sulfamoyl derivatives, which on subsequent deprotection gave the desired compounds in good yields. The structures of compounds 2-4 were confirmed by X-ray crystallographic analysis. All three compounds showed significant antiparasitic activity in vitro, while 2 showed significant activity in vivo against Leishmania donovani and Trypanosoma brucei.
Kini
G D
GD
ICN-Nucleic Acid Research Institute, Costa Mesa, California 92627.
Henry
E M
EM
Robins
R K
RK
Larson
S B
SB
Marr
J J
JJ
Berens
R L
RL
Bacchi
C J
CJ
Nathan
H C
HC
Keithly
J S
JS
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003460:Crystallization; D005872:Giardia / Q000187:drug effects; D006860:Hydrogen Bonding; D007893:Leishmania donovani / Q000187:drug effects*; D051379:Mice; D008968:Molecular Conformation; D015394:Molecular Structure; D010272:Parasitic Diseases / Q000188:drug therapy; D012254:Ribavirin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D012263:Ribonucleosides / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*; D014961:X-Ray Diffraction
D012263:Ribonucleosides; C059925:ribavirin 5'-sulfamate; C062435:1-(5'-O-sulfamoyl-beta-ribofuranosyl)(1,2,4)triazole-3-thiocarboxamide; C062436:1-(5'-O-sulfamoyl-beta-D-ribofuranosyl)(1,2,4)triazole-3-carbonitrile; D012254:Ribavirin